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WHEN CHOICE ARRIVES: Competition & Consequences

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Here are the top 5 biosimilar articles for the week of November 4, 2024. 

The Top 5 Biosimilar Articles for the Week of November 4

Articles

For the first time, Skyrizi (risankizumab-rzaa) has replaced Humira (reference adalimumab) as AbbVie’s sales driver, largely due to companies encouraging “product hopping” to avoid competition, creating concerns for the sustainability of the burgeoning adalimumab biosimilar market.

Skyrizi Overtakes Humira: “Product Hopping” Leaves Biosimilar Market in Limbo

Celltrion plans to commercialize 22 biosimilars by 2030, expanding its global presence with robust sales growth driven by core biosimilars and new launches like subcutaneous infliximab.

Celltrion Sets Sights on 2030 With Expanded Biosimilar Portfolio, Market Reach

Henlius and Organon’s pertuzumab biosimilar met phase 3 goals; Meitheal expanded its US biosimilars; Celltrion’s subcutaneous infliximab (Zymfentra) showed monotherapy could be as effective as combination therapy for inflammatory bowel disease.

Eye on Pharma: Henlius, Organon Updates; Meitheal Portfolio Expansion; Celltrion Zymfentra Data

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The prevalence of inflammatory bowel disease (IBD; Crohn disease and ulcerative colitis) is rising, approaching 1% in Europe and North America. According to a recent 

, alongside this increase in prevalence, health care costs associated with IBD are also rising. The authors said that increase in prevalence combined with shifts in IBD care and higher hospitalization costs is increasing the burden on health care systems. They discussed the challenges to making IBD costs sustainable and strategies toward achieving personalized, cost-effective care for IBD.

Direct and Indirect Costs Associated With IBD

Direct costs associated with IBD include ambulatory visits to gastroenterologists, emergency department visits, admissions for hospitalization or surgery, diagnostics, and medications. Although hospitalization rates have decreased, direct costs have not because of a trend toward more complex disease with greater severity, and rising costs of inpatient care. The authors cited The Lancet Gastroenterology & Hepatology Commission which estimated direct health care expenses associated with IBD are $9,000 to $12,000 per person per year in high income regions. However, they noted “these estimates do not fully account for factors such as disease severity, accessibility, and variability in health care infrastructure among regions.”

They also described the US as an “outlier” in direct health care costs. In the US, drug prices on average exceed international prices by several-fold due to a lack of nationwide price regulation, the fragmentation of the health care system, prolonged market exclusivity periods, and confidential rebates negotiated between private insurers and pharmaceutical manufacturers. “Patients seldom benefit” from these rebates, the authors added.

Indirect costs include lost wages from missing work, reduced capacity at work, early retirement, premature death, delayed workforce entry, and not achieving educational or professional potential. Despite studies attempting to quantify indirect costs, the authors wrote, “many aspects remain poorly understood, leading to an underestimation of their actual impact.”

Challenges to Achieving Cost Sustainability

Challenges the authors cited to reducing IBD costs and achieving sustainability include disparities in access, treatment affordability, underinsurance, and a lack of standardized cost-effective care guidelines. Unplanned health care utilization, for example emergency department visits, “drives much of the cost in IBD care,” they wrote, and cited research suggesting that low-income status leads to less access to timely and effective care, leading to unplanned health care utilization, which has detrimental effects on both long-term health and costs. Also, lower income patients may delay or skip treatments or diagnostics with high out-of-pocket costs.

Strategies the authors recommended to reduce costs included early implementation of biologics, a focus on cost-effectiveness in settings with limited resources, and promoting the use of 

. They also recommended several patient monitoring strategies, such as using telemedicine and noninvasive biomarkers of disease activity. In addition to treatment strategies, such as 

 when appropriate, they recommended support strategies, such as using multidisciplinary care models that provide holistic care, promoting healthy lifestyle behaviors, and recognizing barriers to care faced by vulnerable populations. Regarding settings with limited resources, they commented that there are no guidelines for de-escalating or withdrawing biologics, which could help to reduce costs if developed.

There is a “clear benefit” for achieving remission to a top-down approach of starting biologic therapy early, the authors said. However, less than 20% of private insurance companies in the US permit biologics as a first-line therapy for IBD. They added that based on data from Canada and the Netherlands, whether cost savings from avoided hospitalizations and surgeries outweigh the costs of biologic drugs is unclear.

Biosimilars Limited by Patent Thickets and Market Dynamics

Biosimilar uptake in the US has been “relatively modest,” the authors said. One reason is patent thickets created by originator manufacturers to extend market exclusivity, which have limited market entry of biosimilars. Additionally, after market entry, reimbursement dynamics have limited biosimilar uptake, as manufacturers of originators often offer confidential discounts to payers to outcompete biosimilars.

Addressing the increasing direct and indirect costs of IBD “demands a comprehensive strategy, tackling disparities, access barriers, and cost-effectiveness of therapeutics,” the authors wrote. They added that policy reforms to improve access to IBD care will also be required: for example, reforming prior authorization processes, enhancing drug price transparency, and introducing value-based reimbursement structures.

Burisch J, Claytor J, Hernandez I, Hou JK, Kaplan GG. The cost of inflammatory bowel disease care - how to make it sustainable. 

. 2024:S1542-3565(24)00729-8. doi:10.1016/j.cgh.2024.06.049

Clinical

Business & Practice

Making the Cost of IBD Care Sustainable

The future of a sustainable biosimilars market in the US depends on strategic legislative reforms, improved education for stakeholders, and a robust reimbursement framework that together enhance accessibility, build confidence, and ensure long-term cost savings in health care, according to a panel of industry leaders.

With $36 billion saved in 2023 and nearly 3 billion days of patient therapy delivered without any clinically significant differences from originator biologics, biosimilars are proving their value in the health care space. The panel discussion took place at the 

 and included representatives from 3 biosimilar manufacturers (Sandoz, Teva Pharmaceuticals, Biocon Biologics).

During the discussion, Sonia Oskouei, PharmD, vice president and US head of biosimilars and specialty at Sandoz, emphasized that true accessibility and sustainability in the US market will require a strategic focus on education and policy that supports patients and providers.

Oskouei, who has a decade of experience working with biosimilars, discussed the critical need for expanding biosimilars across various therapeutic areas, referencing the recent approvals for the first denosumab and aflibercept biosimilars.

 She pointed to the journey from biosimilars being in niche oncology markets to mainstream use, adding that more can be done to sustain this growth by streamlining approval processes and educating the public.

Meanwhile, Mary Pietryga, vice president of global marketing at Teva Pharmaceuticals who has 3 decades of experience working in biopharmaceuticals, described the challenges in expanding biosimilar uptake. Patient and provider education gaps, she noted, continue to limit the full realization of biosimilars’ benefits, and improved awareness could accelerate adoption and cost savings.

Joshua Salsi, head of North America commercial at Biocon Biologics, emphasized that the complexity of the US health care market demands a reimbursement model that balances affordability with high-quality standards. Although interchangeability is a legal designation for biosimilars, he explained, it has not become a deciding factor for providers, who are more focused on therapeutic similarity. The discussion emphasized that clearing up misconceptions about interchangeability is essential to driving confidence in biosimilars.

The conversation also touched on legislative factors, with moderator Craig Burton, senior vice president of policy and strategic alliances for the Association for Accessible Medicines and executive director of the Biosimilars Council, discussing the impact of recent policies. Legislative reforms, the panel agreed, are key to supporting the biosimilars market, as streamlined processes can help reduce economic pressures and improve biosimilar accessibility. Oskouei highlighted that by bolstering FDA resources, legislation could enable faster evaluations and approvals, fostering a more competitive and sustainable market.

The role of pharmacy benefit managers (PBMs) emerged as a critical topic. Pietryga and Salsi outlined the challenges biosimilar companies face in navigating PBM contracts, which often favor established biologics. They noted that if the market could encourage more competition among PBMs, biosimilars would have a better chance to compete fairly. Oskouei reiterated that increasing understanding about PBMs’ role and impact could benefit all stakeholders and improve patient access.

"The reality is, especially over the last 5 years, as more [innovator] biologics and the biosimilars to those biologics are being introduced into the marketplace, the US specifically is performing as a high grip market…. Decreasing the cost and time of your resource allocation to get these molecules to market is critical. Ensuring the marketplace to launch these assets into is also critical. I think that we truly are this inflection point to ensure that the success and the adoption of biosimilars continues to have the utmost sustainability moving forward,” commented Salsi.

Lastly, the panel discussed the implications of the Inflation Reduction Act (IRA). Pietryga detailed that while the IRA’s cost-saving intentions are commendable, its effects might limit biosimilar competitiveness unless paired with sustainable reimbursement.

“You have really beneficial payers, and they're aligned to PBMs and specialty pharmacies, and they each take 1 manufacturer. So, you end up with a winner-takes-all scenario…. Ultimately, over time, you could see some players exiting the market, or starting to see some of the big players exit. The hope [in the beginning] was to have an array of manufacturers be able to create this competitive market but now it’s like we’ve gone to the other extreme,” Pietryga explained.

Salsi echoed this, stressing that policy makers should carefully consider the economic environment biosimilars require to thrive. Oskouei added that an education strategy is vital to ensuring all stakeholders—patients, providers, and policy makers—understand the value biosimilars bring.

The session concluded with a call for collaborative action. Pietryga emphasized a united industry approach to overcome market challenges. Salsi reiterated the need for a robust reimbursement model and ongoing education, while Oskouei advocated for innovation and comprehensive educational efforts to bridge gaps in understanding. With continued dedication to these goals, biosimilars are positioned to make high-quality, affordable therapies more accessible, ultimately contributing to a sustainable health care future.

Oskouei concluded with a look toward the future: “It's a ‘circle of biological life’ that biosimilars enable, so you bring healthy competition, lower costs, and ensure the accessibility of critical biologics. But equally important and equally exciting to me is reusing savings realized from biosimilars to invest in the next generation of innovation. So, we can move away from supportive care to disease-modifying treatments to more curative treatments that are better than everything we have available to us today.”

1. Burton C, Oskouei S, Pietryga M, Salsi J. Biosimilars market leaders discussion. Presented at: GRx+Biosims; October 21-23, 2024; Rockville, MD.

2. Jeremias S. FDA approves first denosumab biosimilars. The Center for Biosimilars

. March 5, 2024. Accessed October 31, 2024. 

https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

3. Jeremias S. FDA approves first Eylea biosimilars. The Center for Biosimilars. May 20, 2024. Accessed October 31, 2024. 

https://www.centerforbiosimilars.com/view/fda-approves-first-eylea-biosimilars

By expanding educational initiatives to clarify biosimilar safety, efficacy, and interchangeability, stakeholders can foster trust, improve access, and ensure that biosimilars are widely accepted as high-quality, cost-effective alternatives to originator biologics.

Conference

Panelists Stress Stakeholder Education to Build Confidence in Biosimilars

During a fireside chat at GRx+Biosims, FDA Commissioner Robert Califf, MD, shared his perspective on key challenges and sustainability concerns in the generic drug industry, touching on pressing issues within the US health care system and broader global supply chain vulnerabilities.

“We need to have a much more robust system to continue to learn and employ, in the complex bioscience space, the supportive elements from the clinical, real-world ethics studies. It’s been very important in helping the clinical world see that [generics and biosimilars] are okay,” Califf said.

The conversation was moderated by David Gaugh, RPh, executive vice president of the Association for Accessible Medicines (AAM). The AAM’s 

 was held from October 21 to October 23, 2024, in Rockville, Maryland.

Emphasizing the influence of financialization on health care, Califf described how complex financial incentives, and the concentration of resources negatively affect the resilience of the system. He noted the vulnerability exposed by recent hurricanes, highlighting how such events disrupt critical supplies and underscore the need for a fair pricing structure that sustains the industry. Califf stressed that ensuring high quality in generic drugs requires the government to play an active role in enforcing purchasing criteria based on quality.

On the topic of global supply chain vulnerabilities, Califf addressed the risks associated with the concentrating production of a product to a single location, especially in light of the devastation seen in the Asheville, North Carolina, area after Hurricane Helene hit in September 2024.

 The storm led to the closing of a factory in nearby Marion, North Carolina that served as one of the largest suppliers of intravenous fluids in the country.

 Califf questioned the wisdom behind having a single factory be the main supplier of a particular medical device for the whole country in the first place, especially as unexpected weather events as a result of climate change become more commonplace.

He emphasized the need for government access to supply chain data to help prevent crises and improve coordination, drawing a comparison to the way financial data is managed. Califf also criticized the biopharmaceutical industry's resistance to sharing this vital data, advocating for a more collaborative approach to ensure better preparedness and resilience.

“There's too much at stake if something goes wrong, and it shouldn't have to be that we're scrambling around on the telephone to figure out who else is making certain quantities of supply. But the industry has opposed us getting the information we need with their [lobbying organizations]. And I think that's a really irresponsible approach,” he stated.

Califf also highlighted the potential of artificial intelligence (AI) in improving public health, particularly in supply chain management. He advocated for AI's role in monitoring supply chain integrity and identifying dishonest practices, highlighting efforts the FDA is doing to incorporate these tools into drug application reviews.

“You apply AI for a [drug] application, you’ll find out when people are cheating. And if you’ve cheated in the past, watch out, because it's going to be easy to apply AI…." Califf warned. "I don't like being a cop, I don’t have much insight in developing influence, but I also don't like people who cheat. The system is very dependent on the integrity of the industry, so if you're cheating now, we're going to be applying the AI to you."

Alongside AI, Califf discussed user fees' role in funding FDA activities, noting that they provide strategic insight into future demands while enabling more disciplined operations.

Addressing the future of the generic drug industry, Califf stressed the importance of its role in providing affordable, high-quality treatments for chronic diseases, with a growing global demand for these medicines. He underscored the need for expanded production capacity in diverse locations, adherence to stringent quality systems, and investment in scientific advancement to uphold drug integrity. Concluding with advice for industry stakeholders, Califf emphasized the importance of conducting clinical studies through reputable organizations, fostering honesty, integrity, and collaboration to strengthen the industry's impact on global health. He extended gratitude to the industry for its ongoing efforts and reaffirmed the value of transparency and partnership in advancing public health goals.

“Most of the highly effective drugs have a generic now. As you develop more biosimilars for more users at a lower price, that’ll be a big needle push. So, for the 340 million people in the US, the generic drug industry is robust, but the growth potential worldwide for high quality generics [and biosimilars] is profound, and I think it's one of the most important aspects of public health."

1. Califf R, Gaugh D. Fireside chat with FDA Commissioner. Presented at: GRx+Biosims; October 21-23, 2024; Rockville, Maryland.

2. Reback S. Hurricane Helene: a disaster no one saw coming. The Assembly. October 1, 2024. Accessed October 25, 2024. 

https://www.theassemblync.com/essays/hurricane-helene-disaster-asheville/

3. Lupkin S. Storm damage closes N.C. factory that makes vital hospital supplies. NPR. October 4, 2024. Accessed October 25, 2024. 

https://www.npr.org/sections/shots-health-news/2024/10/04/g-s1-26383/iv-fluids-shortage-baxter-hurricane-helene

At the GRx+Biosims conference, FDA Commissioner Robert Califf, MD, stressed the urgent need for data transparency in the global supply chain and the role of collaboration and artificial intelligence in ensuring the resilience of biosimilar and generic drug production.

Strengthening the Supply Chain: Key Insights From FDA Commissioner Dr Robert Califf

A study of the Veterans Health Administration (VHA) detailed their experience with infliximab biosimilars in a population of patients with inflammatory bowel disease (IBD) who were naive to infliximab.

It took approximately 6 months for the biosimilar infliximab-dyyb (Inflectra) to become the predominant infliximab product for the IBD population after it was added to the Veterans Affairs National Formulary (VANF) in May 2017. In September 2018, infliximab-abda (Renflexis) became the VANF infliximab product, and was rapidly adopted. According to the authors, the rapid adoption of infliximab-abda “may represent increased comfort due to experience with [infliximab biosimilars] among gastroenterologists, accumulating evidence in support of biosimilars, and swift and systematic action by the VHA pharmacy benefit manager to deploy and enforce a VANF compliance initiative.”

Infliximab was the first tumor necrosis factor (TNF)-α inhibitor approved in the US for IBD. The authors noted that although infliximab induces mucosal healing and improves quality of life in patients with IBD, it is expensive, and the introduction of infliximab biosimilars is predicted to reduce costs for the VHA and other health systems. Infliximab-dyyb (Inflectra) was approved by the FDA in April 2016 and infliximab-abda (Renflexis) in April 2017 for all indications of the reference product, and the approval for IBD (Crohn disease and ulcerative colitis) was via extrapolation. Although gastroenterologists were “initially cautious” about biosimilars approved through extrapolation, accumulating research “continues to provide reassuring data that biosimilars are effective, safe, and comparable to reference biologics,” the authors wrote However, they added that most studies have focused on infliximab-dyyb, not infliximab-abda, and few studies have examined real-world utilization of infliximab biosimilars in the VHA.

The descriptive cohort study investigated infliximab utilization patterns in infliximab-naive patients with IBD during their first 365 days of treatment. Using the VHA Corporate Data Warehouse, 1763 patients receiving care in the VHA initiated on an infliximab product between September 2016 and December 2019 were identified and included in the study, 785 receiving the reference product, 441 receiving infliximab-dyyb, and 537 receiving infliximab-adba.

In baseline criteria, there were differences between groups in missing ethnicity data, and in the proportion of former smokers. Among patients initiating infliximab-abda, 42% were former smokers, compared to 33% initiating infliximab-dyyb and 32% initiating the reference product.

Adoption of Infliximab-dyyb Was Slower Than That of Infliximab-abda

Infliximab-dyyb was used for at least half of new infliximab prescriptions by 183 days after addition to the VANF and took 335 days to become the predominant product in the VHA, whereas infliximab-abda became the predominant infliximab product within 90 days.

Differences in product dosing were found between groups, specifically in average accumulative dose (reference product, 3232 mg; infliximab-dyyb, 3204 mg; and infliximab-abda, 3641 mg) and maximum dose (reference product, 576 mg; infliximab-dyyb, 613 mg; and infliximab-abda, 622 mg).

The authors observed differences in measures of adherence and persistence on the index treatment. However, the greater adherence and persistence observed for infliximab-abda compared to infliximab-dyyb and the reference product “appeared to be a result of formulary pressure to switch patients to the current VANF product.” For example, 40% of patients who were not persistent on the reference product and 42% who were not persistent on infliximab-dyyb switched to infliximab-abda. They said that after accounting for switching between infliximab products, “a high proportion” of patients (approximately 60%) who initiated therapy with the reference product or infliximab-dyyb remained on infliximab therapy at the end of the 365-day follow-up period.

No differences in emergency department or inpatient visits were observed between groups, however, there were differences in baseline and follow-up gastroenterologist visits infliximab-abda (3.88; 95% CI, 3.65-4.11), infliximab-dyyb (3.74; 95% CI, 3.50-3.98), and reference infliximab (3.37; 95% CI, 3.19-3.49). These health care utilization measures, including gastroenterologist visits, emergency department visits, and inpatient visits, did not indicate any differences in surveillance patterns, safety, or effectiveness among the groups of infliximab products, the authors said.

There were no differences between groups in IBD-related laboratory measures, including liver function measures, C-reactive protein, fecal calprotectin, lactoferrin, infliximab trough levels, and anti-drug antibodies. However, the authors did note that only 27% to 41% of patients were tested for antidrug antibodies.

The authors concluded that infliximab utilization and laboratory measures were similar between infliximab-abda, infliximab-dyyb, and the reference product in patients receiving care from the VHA for IBD.

Patel S, Walsh J, Pinnell D, et al. Real-world experience with biosimilar infliximab-adba and infliximab-dyyb among infliximab-naïve patients with inflammatory bowel disease in the Veterans Health Administration. 

. 2024;103(37):e39476. doi:10.1097/MD.0000000000039476

A study of the Veterans Health Administration detailed their experience with infliximab biosimilars in a population of patients with inflammatory bowel disease (IBD) who were naive to infliximab. 

Veterans’ Experience With Infliximab Biosimilars for IBD Treatment

Sophia Humphreys talks

In an interview, Sophia Humphreys, PharmD, discusses how the expansion of biosimilars into new therapeutic areas, such as immunology, endocrinology, and ophthalmology, has led to increased hesitance compared to the quicker adoption seen in cancer treatment. This is due to the maintenance nature of many therapies, making it harder to switch patients to biosimilars. 

She emphasizes the need for patient and provider education about the safety, efficacy, and similarity of biosimilars. When addressing adalimumab biosimilars, Humphreys highlights factors such as product formulation preferences, interchangeability regulations, and payer coverage as key drivers in market competition.

This transcript has been edited for clarity.

How do new therapeutic classes and indications for biosimilars influence market expansion?

I think this goes beyond just patient education. And, for example, when we started with just the cancer curative and supportive agents, biosimilars, those are quickly adopted, and once we start to move into immunology, endocrinology and ophthalmology, now we started to observe more hesitance. 

One reason is because a lot of these are maintenance therapies. So we're not looking at starting a new treatment plan or starting a new cycle treatment with a new biosimilar. We're looking at convincing a patient who has failed several therapies before they reach the [reference] biologics now that could convince them to switch to a biosimilar product. So the first thing is that we really wanted to educate both our patients as well as our providers that these products are highly similar to the reference product. 

There's no evidence of diminished efficacy or increased immunogenicity or safety signals so far. For the past 10 years, we have used biosimilar successfully. And also we really wanted to address our health care system leaders that these biosimilar product in the expanded therapeutic classes would really increase access of care—really providing life saving, life altering medications for more patients.

What are the key factors driving competition among adalimumab biosimilars in the market?

Adalimumab, that's everybody's favorite molecule since July of 2023. So, several factors. This is actually quite similar—adalimumab and infliximab. It's almost similar. For autoimmune disease, as we have mentioned, a lot of patients are on maintenance [therapies]. And adalimumab has so many product [options]. And you really want to see if the product can match the existing product that our patient are using as much as possible. 

For example, if my patient is using a citrate-free product, you probably don't want to switch them to a product that is not citrate-free, which will cause probably more injection site discomfort. And also, a lot of patients prefer higher concentration vs lower concentration. That's another concern. And interchangeability is another concern. 

In a lot of states, we allow pharmacy-level switch, which means when a physician's order is the reference product for adalimumab in the state where they allow pharmacy-level switch, a pharmacist can switch the particular product to a interchangeable biosimilar of the reference adalimumab without a new authorization from the physician who prescribed that originator, because this particular product is interchangeable. 

Of course, different states have different regulations, and you also need to make sure that you meet the communication and information sharing requirement of your state, which means the patient needs to know that you're giving them a different product. The physician would need to know when you did the switching and which product was provided to the patient. Of course, most importantly, we need to know if the biosimilar you are switching to is covered by the patient's payers, and if they provide similar or comparable patient support and especially copay assistance. 

And when we are working with 340B-eligible sites, you would need to consider the switching effect to your 340B accumulation. So, a lot of factors are brought into this consideration. It's a very comprehensive analysis.

Sophia Humphreys, PharmD, from Sutter Health explains that expanding biosimilars into new therapeutic areas faces hesitance due to maintenance therapies, emphasizing the importance of education.

Addressing Hesitance in Biosimilar Adoption

 in patients with moderate to severe plaque psoriasis confirmed similarity of the proposed ustekinumab biosimilar SB17 (Samsung Bioepis) to the reference product (Stelara) in efficacy, safety, pharmacokinetics, and immunogenicity.

Most biologics for inflammatory diseases, including psoriasis, are inhibitors of tumor necrosis factor (TNF)-α, but ustekinumab is the first of newer biologics focused on other targets, the authors said. Ustekinumab, an inhibitor of interleukins 12 and 23, is used to treat psoriasis, psoriatic arthritis, and inflammatory bowel disease. The authors cited advantages of ustekinumab over anti-TNF biologics, such as less frequent dosing and “perhaps a better safety profile.”

 has previously been shown to be similar to the reference product in physicochemical characteristics and pharmacokinetics in healthy human subjects. The current study assessed clinical efficacy, safety, pharmacokinetics, and immunogenicity compared to reference ustekinumab for 28 weeks in moderate to severe plaque psoriasis.

The phase 3, double-blind, randomized controlled trial was conducted in 45 centers across 8 countries. Subjects (n = 249) were randomized to receive SB17 or the reference product at 0 weeks, 4 weeks, then every 12 weeks until week 40. The primary endpoint was percent change from baseline in Psoriasis Area and Severity Index (PASI) at week 12, and additional endpoints were measured through week 28.

The adjusted difference in PASI change from baseline at week 12 was –0.6% (95% CI, –3.780 to 2.579), within the predefined equivalence margin of –5% to 15%. The authors commented that the time-response curve of percent change of PASI from baseline was “nearly identical” between groups up to week 28. Secondary efficacy endpoints, including Physician's Global Assessment and Dermatology Life Quality Index were “also comparable” between the biosimilar and reference product groups.

Overall incidence of treatment-emergent adverse events (TEAEs) was 48% in the biosimilar group and 49% in the reference product group. According to the authors, most were mild to moderate and not considered related to the study drugs. The most frequently reported TEAEs were nasopharyngitis, COVID-19, and upper respiratory tract infections. Six participants (2.4%) in the biosimilar group and 3 (1.2%) in the reference product group experienced serious TEAEs, but none were considered related to the study drugs. There were no deaths, and 1 TEAE in the reference product group (hepatic steatosis) that led to discontinuation of the study treatment. TEAEs of special interest occurred in 28% of patients receiving the biosimilar and 30% of those receiving the reference product, and most were infections.

The pharmacokinetic profiles were “generally comparable” between groups, the authors said. Incidence of anti-drug antibodies was lower in the biosimilar group at 13%, compared to 39% in the reference product group, and incidence of neutralizing antibodies was 14% and 35%. However, the primary efficacy outcome was comparable between groups in ADA-positive and ADA-negative subgroups, the authors commented, adding that the difference in ADAs could be due to differences between the cell lines that produce the 2 monoclonal antibodies. They noted that similar differences in immunogenicity compared to the reference product have been cited for other ustekinumab biosimilars, and “lower immunogenicity does not preclude biosimilarity if the ADA-negative subgroups of the biosimilar and the originator have similar efficacy.”

The author concluded that SB17 was clinically similar to the reference ustekinumab up to week 28, with comparable safety and pharmacokinetic profiles.

Feldman SR, Narbutt J, Girolomoni G, et al. A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis. 

. 2024;91(3):440-447. doi:10.1016/j.jaad.2024.04.045

A phase 3, 28-week comparative clinical trial in patients with moderate to severe plaque psoriasis confirmed similarity of the proposed ustekinumab biosimilar SB17 (Samsung Bioepis) to the reference product (Stelara) in efficacy, safety, pharmacokinetics, and immunogenicity. 

Samantha DiGrande

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